The objective of the proposed investigation is to use normal and malignant tissues in the mouse to obtain information of potential use to clinical radiotherapy in three distinct areas. The three basic areas are: (1) A study of the influence of commonly used chemotherapeutic agents on the radiation tolerance of three normal tissues, the spinal cord, the lung and the kidney, (2) testing of highly promising electron-affinic agents for their ability to radiosensitize tumors, and an investigation of ways to enhance the cytotoxicity of these agents to tumor cells, and (3) a study of metastases, with an emphasis on the important mechanisms involved in the process, and a study of how various treatments of the host can affect spread from the primary tumor. The chemotherapeutic agents to be used with the normal tissue endpoints are - with radiation myelitis: BCNU and misonidazole; with radiation pneumonitis: actinomycin D, adriamycin, bleomycin and cyclophosphamide; and with radiation nephritis: actinomycin D, cis-platinum and cyclophosphamide. For the normal tissue and the hypoxic cell sensitizer studies ((1) and (2) above), the conditions of testing will be as close to the clinical practice of radiotherapy as can be obtained; namely, multifraction dose regimens will be used, and the normal tissue effects to be studied - radiation myelitis, pneumonitis and nephritis - are all late responses to radiation which can limit the dose that can be administered to a tumor. In the tumor studies, tumor control (TCD50) and regrowth delay will be the important endpoints. In the study of metastases, both an immunogenic and a non-immunogenic tumor/host system will be employed, and various commonly used treatments of the host (e.g., lung irradiation, systemic chemotherapy) will be performed to determine their influence on metastatic spread via both the bloodstream and the lymphatics.